WO2002049548A1

WO2002049548A1 - Indwelling instrument

Info

Publication number: WO2002049548A1
Application number: PCT/JP2001/000202
Authority: WO
Inventors: Yuichi Mori; Hideo Nakajima; Yasuharu Noishiki; Yuichi Higuchi; Shigeki Honzu
Original assignee: Yuichi Mori; Hideo Nakajima; Yasuharu Noishiki; Yuichi Higuchi; Shigeki Honzu
Priority date: 2000-12-21
Filing date: 2001-01-15
Publication date: 2002-06-27
Also published as: AU2001225537A1; JP2002306518A

Abstract

An indwelling instrument which is light-weight, has an excellent mechanical property, and is excellent in joining capability with respect to in-vivo tissues to thereby contain in at least part thereof a metal portion, wherein at least part of the metal portion is composed of a porous metal.

Description

Specification

Indwelling device

TECHNICAL FIELD The present invention relates to an indwelling device that can be indwelled (or placed) in a body by an operation such as transplantation, typically, for example, a medical device (for example, a surgical device (orthopedic surgery, brain surgery, etc.) or a dental device that can be used in a dental region) Medical devices usable in the field of orthopedic surgery, such as artificial bones that can be implanted into hard tissues such as bones, plates for fixing fractures, screws and wires, and clips and brains for ligating cerebral aneurysms Medical tools such as a coil for filling an aneurysm that can be used in the field of brain surgery; medical tools that can be used in the dental field such as artificial dental roots, and stents).

The indwelling device according to the present invention has a stable state for a long period of time while achieving weight reduction and compatibility with internal tissues (preferably, further promoting healing, preventing infection, etc.) without reducing strength. Can be placed in the body.

One aspect of the indwelling device according to the present invention relates to a stent, and particularly, to patency the lumen (eg, blood vessel, bile duct, bronchus, urethra, digestive tract, etc.) narrowed or obstructed by a lesion. About the stent to be made.

The stent of the present invention has various functions (for example, anti-thrombotic properties, hyperinhibition of intimal hyperplasia) while minimizing the weakening of the stent itself or peeling of the coating substance from the stent body as much as possible. ) Is extremely easy. Thus, the stents of the present invention can be used, for example, for acute coronary occlusion or re- It can be particularly suitably used for an intervention therapy for stenosis.

Further, the stent of the present invention can be suitably used in a treatment method for maintaining the patency of a lumen obstructed or narrowed by cancer or the like, utilizing the ease of imparting the function. Background art

The application site and application method of the indwelling device of the present invention are not particularly limited, but for convenience of explanation, a conventional technique will be described using an example of “implanted device” which is a typical use method of the indwelling device in recent years.

With respect to implantable devices in orthopedic and dental fields, many such devices are made of metal. Metals are used for these because of the expectation of mechanical strength for metal materials. In response to these expectations, metallic materials have greatly contributed to the treatment of many diseases that were considered difficult to treat.

Especially in the areas of metal plates, screws, wires, etc., which can be used for artificial joints, artificial bones, artificial roots, and fracture treatments, metallic materials were the sole materials of their own. In addition, cerebral aneurysm ligation clips and cerebral aneurysm filling coils used in the cerebral vascular region are also made of metallic materials because of their stability in the body, excellent mechanical strength, and good workability. Has been used. Stainless steel, titanium, platinum, tantalum, nickel / titanium alloys and shape memory alloys have been mainly used as metallic materials to be kept in the body.

However, in today's medical care, further expectations are placed on metal materials, and in addition to the existing strength, suppleness, durability against continuous stimuli, stealth in the body, corrosion resistance, non-irritability, etc. , Higher quality, for example, biological function and physical properties equivalent to body tissue material, body tissue Highly functional elements such as interaction with cells at the cellular level have come to be required.

However, today's metallic materials cannot meet these requirements. In addition, metallic materials typically show large differences in their balance in volume, weight, mechanical properties, etc. compared to those of body tissue, so simple conditions (eg, However, the problem of creating materials that are closer to body tissue remains unsolved.

In the past 30 years, the challenge that has been given to metal materials in the past 30 years is the affinity for tissue in the body, and the affinity with cells has been improving through the use of titanium and other materials and improvements in surface treatment such as ceramic processing by plasma irradiation. Was. However, no further improvements have been made. The main cause may be that metal materials did not have an improvement means to fundamentally solve many of these problems. This leaves some adverse clinical phenomena neglected. For example, prosthesis in the elderly; plates, ports, and wires that fix hip joints, artificial heads, or fractures are too strong in metallic material and are too heavy to wear or destroy the patient's own bones Or inconvenience such as breaking. In addition, in conventional dental implants, the gingival fibers did not bind to the attachment, and bacteria could easily enter.

Furthermore, since it is impossible for tissue of the body to enter the metal material, when inserted into the body, the body tissue surrounds the entire metal material with the tissue of the body and “encapsulation, encapsulation” This phenomenon represents an extraterritorial jurisdiction within a single country, so if an infection occurs, even if a drug such as an antibiotic is used, Difficult to enter the territory, therapeutic effect is uncertain Be fruitful.

If a small part of the metal is infected, the metal material is extremely vulnerable to infection, because the infection spreads rapidly to the entire surface of the material at the boundary area between the inner surface of the encapsulated tissue and the material. Also results.

On the other hand, it is not possible to impart properties to conventionally used metal materials that positively act on the tissue of the body, for example, promote healing, antibacterial, anticoagulant, and anticoagulant. , Almost impossible. For example, platinum or the like has been used as a medical device that is inserted into a blood vessel such as a filling coil in a cerebral aneurysm and used as an embolizing agent, but the thrombus formed on the surface of the platinum coil causes the inside of the aneurysm to be Is occluded, but the process by which the formed thrombus becomes matrix and becomes covered with vascular endothelial cells (vessel endothelization) is very slow and cannot be said to be complete treatment, and the thrombus is released into the cerebral vein. There was a major problem that the danger would last forever.Of course, even when conventional metal materials were used as the above-mentioned artificial bones, fracture plates, artificial tooth roots, etc., they would positively act on body tissue and promote treatment. However, it was impossible to impart an action to prevent infection.

Further, with respect to the stent which is one embodiment of the indwelling device, the application site and application method of the stent of the present invention are not particularly limited. However, for convenience of explanation, the typical application method of the stent in recent years is “interpension”. Conventional technologies are described using “treatment” as an example.

In recent years, a number of stents have been clinically placed in the coronary artery for interventional treatment of acute coronary occlusion and restenosis after percutaneous coronary angioplasty (PTCA). Regarding the placement of this stent in the coronary artery, the recoil of the coronary artery was significantly reduced, and a good initial dilatation effect was observed. Conventionally, the materials of stents that have been developed are metals, such as stainless steel, tantalum, titanium, and an alloy of titanium and nickel (Nitinol). The structure can be broadly classified into a slotted tube stent having a tubular structure and a coil stent made of a single wire.

Methods for expanding these stents in a lumen such as a coronary artery that is stenotic or occluded include a method using a balloon catheter or the like, a method using a balloon, and a method in which the stent is folded into a catheter or a sheath. And a method of expanding the stent made of nitinol, which is a shape memory alloy, by a temperature change. ing.

As described above, various stents having different structures and / or materials have been developed in accordance with the purpose of use, the method of indwelling, and the like. In the case of PTCA above, acute recoil of the blood vessel after balloon dilatation is observed in most cases when no stent is used. In contrast, the greatest benefit of using a stent is that it significantly reduces vascular recoil, i.e., the use of a balloon Z stent provides a good initial dilation effect of the vessel. .

However, significant problems with the use of conventional stents include: occlusion due to thrombus formation early in the stent placement, and reocclusion or restenosis later in the stesit placement.

It is generally believed that metal, which is the material of the stent, promotes thrombus formation. Stents also tend to cause the reocclusion or restenosis seen weeks to months after their placement, since metal is a foreign body to the body and promotes intimal proliferation. Anticoagulants such as heparin and antiplatelet agents such as aspirin have been systemically administered to prevent thrombus formation due to stent placement, but these methods increase the risk of bleeding. There is a serious problem. '

On the other hand, as a method for preventing thrombus formation due to stent placement, a device for imparting antithrombotic properties to the stent itself has been devised. For example, structures have been devised to minimize the thickness of the stent or the metal surface area of the stent, but there are limitations to mechanically preventing recoil in the blood vessel. .

In addition, a method of polishing a metal surface of a stent smoothly has been performed. According to this method, shear stress caused by local and microscopic turbulence and eddy current generated on the surface of the stent is reduced, and a certain effect on thrombus formation is recognized. It is impossible to stop.

Further, a method of coating the metal surface of the stent with a polymer material having less thrombus formation has been used. According to this method, although some antithrombotic properties can be obtained, it is said that the intimal proliferation that causes restenosis tends to be rather accelerated.

In a similar manner, an anticoagulant such as heparin is contained in the polymer coating layer on the surface of the stent, and the anticoagulant is slowly released into the bloodstream. Attempts have been made to grant. However, when a sufficient amount of drug is contained in the coating polymer layer, the coating thickness is increased, and the blood flow is locally disturbed at the stent placement portion, and conversely, a thrombus tends to be formed. In addition, impregnating a large amount of drug reduces the mechanical strength of the coating polymer layer, and increases the tendency for problems such as peeling of the coating layer from the stent metal surface. On the other hand, attempts have been made to fabricate the stent itself from a polymer material and mix an anticoagulant or the like into the polymer, but there is a major problem in physical strength compared to a metal stent. It has not been put to practical use.

In addition, systemic administration of keloids and tranilast, a therapeutic agent for hypertrophic scars, is a method of preventing intimal hyperproliferation that causes reocclusion or restenosis at the later stage of stenting, or A method using a catheter to locally irradiate the gamma ray or 3 rays to the stent placement part to suppress cell division and proliferation has been performed, and a certain effect has been observed. An activation stent has also been developed in which P-32 is ion-implanted into the stent itself. In addition, drugs such as tranilast, which suppresses the release of tumor growth factor (TGF-), interleukin-1 (IL-1), platelet-derived growth factor (PDGF), etc., during vascular disorders, are used in combination with the aforementioned anticoagulants. As in the case of (1), there is also a method in which the drug is contained in a polymer film coated on the surface of the stent to make it release gradually.

However, in the case of activated stents, handling is a major problem. As described above, the method of coating a polymer layer containing a drug on the stent surface not only increases the thickness of the stent to promote thrombus formation, but also causes problems such as peeling of the coating from the metal surface. Tends to occur.

As described above, various attempts have been made to prevent thrombus formation in the early stage of stent implantation, which is a serious problem with current stents, and to prevent restenosis or reocclusion due to overgrowth of intimal vessels in the late stage. However, none of them are practically satisfactory. At present, the most promising method is to coat the stent surface with an anticoagulant or a polymer material containing a drug that inhibits cell or tissue division and proliferation, and to release the drug slowly. ing. However, at present, if a sufficient amount of the drug is mixed in as described above, the polymer coating layer becomes thicker, and a thrombus is easily formed in a hemodynamic manner. Furthermore, a sufficient amount of the drug is mixed and controlled release is performed. For this purpose, it is essential that the coated polymer material layer has a porous structure, which causes problems such as mechanical strength of the coating layer and peeling from the metal surface.

As described above, if various functions are to be added to conventional stents, even if the functions have been successfully added to some extent, other problems (and in some cases, more serious problems) may occur. In some cases, increasing the risk of the stent itself.

An object of the present invention is to provide a device for indwelling in a body that has solved the above-mentioned disadvantages of the conventional technology.

Another object of the present invention is to provide an indwelling device having the same mechanical properties and excellent strength and lightness as the tissue surrounding the body.

It is still another object of the present invention to provide an indwelling device in which the indwelling device is imparted with affinity and binding with surrounding internal tissues. It is still another object of the present invention to provide a device for indwelling the body, which is provided with positive functions such as healing promotion, antibacterial action, blood coagulation, and anticoagulant action. Still another object of the present invention is to provide a stent that solves the above-mentioned disadvantages of the prior art.

Still another object of the present invention is to provide the stent with various functions (for example, antithrombotic properties, excessive vascular intima, etc.) while minimizing the weakening of the stent itself or the detachment of the coating substance from the stent body. To provide a stent which is extremely easy to impart

Disclosure of the invention The present inventors have conducted intensive studies and found that imparting a porous structure to a metal itself constituting a device for indwelling the body such as a stent is extremely effective for achieving the above object.

The metal indwelling device of the present invention is based on the above findings, and is an indwelling device including at least a part of a metal part, wherein at least a part of the metal part includes a porous metal. It is a characteristic.

The indwelling device of the present invention having the above-described structure is not only lightweight because the porous metal material constituting the device is porous, but also has a remarkably increased contact area with the body tissue, so that sufficient bonding strength can be easily obtained. You can get it.

Further, in the embodiment using a porous metal having an anisotropic pore structure described later, not only the indwelling device has excellent mechanical strength, but also it is easy to show the same toughness as the hard tissue in the body .

Furthermore, in the indwelling device of the present invention having the above-described configuration, since the constituent metal material is porous (especially in the case of a structure of anisotropic pores that are swollen backward), the in-vivo tissue easily enters the inside. Further, it is easy to strengthen the bond between the metallic material and the surrounding body tissue. In this case, it is possible to control the degree of invasion of body tissue particularly by the size of the pore.

When the pore size is 8 to 15 μπι, the body tissue such as collagen fiber is 40 or more. When L is 0 m, the bone-like tissue is, and when it is 150 to 200 μm. It is said that each bone tissue penetrates into the pore. Therefore, precise control of the pore size is critical to strengthening the connection between the device and the surrounding body tissue.

As described above, if the connection between the indwelling device and the surrounding body tissue can be strengthened, for example, even if bone resorption, osteoporosis, or deterioration of bone re-performance occur, The medical device is stably held in the body. For example, in the case of an artificial tooth root, it is easy to obtain a joint strength enough to withstand occlusal force. In the case of a fracture plate, bolt, wire, etc., it is easy to obtain sufficient joint strength.

Furthermore, as described above, even if a small part of the metal surface is infected, if the connection between the metal surface and the surrounding tissue is strong, the infected part is limited to the local area and does not cause a major obstacle.

In addition, in the case of an artificial tooth root, if the bonding between the artificial tooth root and surrounding tissue is strong, adhesion of food plaque (plaque) to the surface of the artificial tooth root due to food debris, bacteria and the like is suppressed. Prevent peri-implantitis.

Furthermore, since the metal material constituting the indwelling device of the present invention having the above structure is porous, various functional substances (for example, drugs such as coagulants, anticoagulants, antibacterial agents, etc., Or a bioactive substance such as an accelerator or a cell, etc., if necessary, in combination with a polymer compound). Therefore, the functional substance can be gradually released from the surface of the medical device into the surrounding tissue, and healing promotion, antibacterial, anticoagulant, and anticoagulant effects can be positively imparted to the medical device. Is possible.

In particular, in an embodiment using a porous metal having an anisotropic pore structure described later, since the pore is an open type, it is possible to fill a large amount of a functional substance inside the porous metal and to release the porous metal gradually. It will be easier. When a cell growth promoting substance is used as the above-mentioned functional substance, for example, by gradually releasing the substance from the indwelling device of the present invention in the form of a filling coil in a cerebral aneurysm, It is possible to significantly promote the delay of vascular endothelialization, which has been a critical problem in the past.

In addition, the plate of the present invention in the form of a plate for fixing a fractured part and an artificial tooth root is used. The sustained release of cell growth-promoting factors and the like from the placement instrument can significantly enhance healing. In addition, when an antibacterial agent or the like is used as a functional substance, it is possible to positively prevent infection, which was a major problem with artificial joints and artificial dental roots.

In the present invention, in the aspect in which the direction of the pores of the porous metal is aligned in one direction (S maxZ S min ≥2), and the shape of the cross section of the port T in a direction perpendicular to the direction is close to a circle, By maintaining the strength, it becomes easier to express sufficient strength to the artificial joint, the plate for fixing a fractured part, the screw, the artificial tooth root, and the like of the present invention.

In the present invention, in the aspect in which the pore inner surface of the porous metal is formed by the solid solution strengthening layer or the ceramic layer, the strength of the porous metal can be easily further improved.

In the embodiment of the present invention, in which the porous metal is produced using a metal-gas system and utilizing the difference in solubility of gas atoms in a molten state and a solidified state of the metal, the porous metal is maintained at a different strength while maintaining the strength of the porous metal. It is extremely easy to obtain an isotropic pore. In such an embodiment, the solid solution strengthening layer can be easily formed on the inner surface of the pore by the reaction between metal atoms and gas atoms in the porous metal production process.

In the present invention, if necessary, a ceramic layer can be formed on the inner surface of the pores of the porous metal by a chemical vapor deposition method or a physical vapor deposition method. Such a ceramic layer on the inner surface of the pore can also be formed by ion implantation.

In the case where the stent according to one embodiment of the present invention having the above-described configuration is used, the stent is configured while suppressing weakening of the stent itself or peeling of the coating substance from the stent body as much as possible. Extremely easy to fill non-metallic material into porous metal pores It is. Therefore, as the nonmetallic substance, various functional substances such as organic substances (for example, agents such as anticoagulants, anticancer agents, and antibacterial agents, physiologically active substances such as cell growth suppressing or promoting agents, or cells; (Combined with a polymeric material, if necessary) is extremely easy to fill. 、 On the other hand, in the stent of the present invention, the porous metal itself constituting the stent has a porous structure. In addition, peeling of the coating substance from the stent body can be suppressed as much as possible.

In the embodiment of the present invention in which the pore of the porous metal is open, it becomes easier to release the drug or physiologically active substance filled in the pore from the surface of the porous metal.

In the present invention, in the aspect in which the pore direction of the porous metal is aligned in one direction and the shape of the pore cross section in a direction perpendicular to the direction is close to a circle, the strength of the porous metal is maintained by maintaining the strength of the stent. It becomes even easier to develop and maintain sufficient strength to prevent recoil of blood vessel walls and the like. .

In the present invention, in the aspect in which the pore inner surface of the porous metal is formed by the solid solution strengthening layer or the ceramic layer, the strength of the porous metal can be further improved.

In the aspect of the present invention, the porous metal is manufactured using a metal-gas system using the difference in solubility of gas atoms between the molten state and the solidified state of the metal, and while maintaining the strength of the porous metal, It is extremely easy to obtain a sex pore. In such an embodiment, the solid solution strengthening layer can be easily formed on the inner surface of the pore by the reaction between the metal atom and the gas atom in the porous metal manufacturing process. '' In the present invention, chemical vapor deposition or physical It is also possible to form a ceramics layer on the inner surface of the pores of the porous metal by a conventional vapor deposition method. Such a ceramic layer on the inner surface of the pore is formed by an ion planter. It is also possible to form by a method of drawing.

FIG. 1 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial joint.

FIG. 2 is a schematic plan view and a schematic cross-sectional view showing an example in which the indwelling device according to the present invention is in the form of a fracture portion fixing plate.

FIG. 3 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of a screw for fixing a fractured part.

FIG. 4 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial tooth root.

FIG. 5 is a schematic perspective view showing an example of a method for producing a hollow cylindrical sample for measuring pore directionality (S max / S min) of a porous metal. FIG. 6 is a schematic perspective view showing an example of a method for producing a plate-like sample for measuring the pore directionality of porous metal.

FIG. 7 is a schematic perspective view showing an example of a method for producing a laminated sample for measuring the pore directionality of a porous metal.

FIG. 8 is a schematic cross-sectional view showing an example of a measurement method for measuring the pore directionality of a porous metal.

Figure 9 shows the σ / σ of “Lenton-type” porous copper manufactured using the metal-gas method. It is a rough showing an example of the relationship between (relative tensile strength) and porosity.

FIG. 10 is a schematic cross-sectional view showing an example of a device for producing a linear porous metal. FIG. 11 is a schematic perspective view and a schematic cross-sectional view showing an example of a linear porous metal and an example of a relationship between a pore direction and a cooling direction.

FIG. 12 is a schematic cross-sectional view showing another example of an apparatus for producing a linear porous metal.

Fig. 13 is a graph showing an example of the relationship between the nitrogen partial pressure and the argon partial pressure of the mixed gas in the porous metal production method by the metal-gas method. Fig. 14 corresponds to one condition of the graph in Fig. 13. A micrograph (magnification: 2.6 times) of a porous metal cross section obtained by the above method.

FIG. 15 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained corresponding to the other conditions of the graph of FIG.

FIG. 16 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained according to still another condition of the graph of FIG.

FIG. 17 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained under still other conditions in the graph of FIG.

FIG. 18 is a schematic plan view showing one embodiment of the stent of the present invention. FIG. 19 is a schematic plan view showing another embodiment of the stent of the present invention. FIG. 20 is a schematic plan view showing another embodiment of the stent of the present invention. FIG. 21 is a graph of FIG. 3 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained according to one condition.

FIG. 22 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained corresponding to the other conditions of the graph of FIG.

FIG. 23 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained according to still another condition of the graph of FIG.

Figure 24 is a plot of the graph of Figure 13 obtained for yet other conditions. 1 33333333

It is a micrograph (magnification: 2.6 times) of a metal cross section of 469 23578. In the above drawings, the meaning of each symbol is as follows.

2 1 ... crucible

2 2… Heating section

2 3 ... mixed gas

2 4 ... Molten metal

2 5… Cooling section

26. Solidified porous metal wire

3 1 a ... Starting material

3 1 b ... Molten metal

3 1 c ... atmosphere

Crucible ''

Heating coil

Thermal insulator

Heat shield

Pressure vessel

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in detail with reference to the drawings as necessary. In the following description, “parts” and “%” representing the quantitative ratios are based on mass unless otherwise specified. '' (Indwelling device)

In the present invention, the “in-vivo indwelling device” refers to a body by an operation such as transplantation. A medical device that is temporarily or (semi) permanently placed or placed inside. As used herein, "medical device" is intended to be used for the diagnosis, treatment or prevention of human or animal disease, or to affect the structure or function of a human or animal body. It is said that the instrument is supposed to be.

The term “body” refers to a human or animal body. As long as the indwelling body has a significance (for example, preservation of the body tissue and prevention of deterioration), it includes not only the body tissue but also the body of the cadaver. In the present invention, a “body” indwelling device is used as long as at least a part of the indwelling device can be indwelled in a body tissue by invasion, penetration, or the like.

The “medical device” in the present invention is not particularly limited as long as the use of the porous metal is effective. Typical examples of the “medical device” in the present invention include an artificial joint (FIG. 1), a plate for fixing a fractured part (FIG. 2), a screw (FIG. 3), a wire, an artificial root (FIG. 4), a cerebral artery Includes filling coil inside the aneurysm.

(Stent)

In the present invention, the term “stent” refers to a structure that is temporarily or semi-permanently placed inside a lumen to maintain the inner diameter of the lumen. The structure of the stent is not particularly limited as long as it performs such a function.

Examples of shapes applicable to the stent of the present invention include shapes as shown in the schematic development views of FIGS. Figure 1 shows the expanded view of a so-called “multi-link” type stent when it is expanded. This stent can be produced, for example, by forming a shape as shown in FIG. 18 with a wire or the like and then welding it appropriately as shown by the arrow in the figure.

Fig. 19 shows the so-called “Palmats-Shiatsu” type stage. Figure 2 shows a development view of the client when it is expanded. This stent can be produced, for example, by directly “burning” a hollow cylindrical metal material using a laser or the like so that the metal material has a shape when expanded as shown in FIG. Monkey

Fig. 20 shows a developed view of a so-called "wiktor <5X" type stent when it is expanded. This stent can be manufactured by forming a shape as shown in FIG. 20 with a wire or the like, and then appropriately welding the same as in FIG. 18.

(Metal with porous structure) ''

The porous metal constituting the stent of the present invention is not particularly limited as long as it has porosity, but those having the following physical properties can be particularly preferably used.

(Metal with porous structure)

The porous metal constituting the indwelling device according to the present invention is not particularly limited as long as it has porosity, but those having the following physical properties can be particularly preferably used.

(Pore size)

The porous metal constituting the indwelling device of the present invention preferably has an average pore size (pore diameter) force of about 0.1 to 100 m, more preferably about 0.5 to 500 μm. Such a pore size is preferably used, for example, by using a measuring device (trade name: Automated Perm-Porometer) manufactured by Porous Materials, Inc. in the United States. It is possible.

(Pore size)

The porous metal constituting the stent of the present invention preferably has an average pore size (pore diameter) of about 0.1 to 50 mm, more preferably about 1 to 20 mm. Such a pore size is, for example, US Porous M It is suitable for use with a measuring device manufactured by aterials, Inc. (trade name: Automated Perm-Porometer). (Porocity)

The porous metal forming the indwelling device of the present invention preferably has a porosity (porosity or porosity) of about 5 to 80%, more preferably about 10 to 40%. Such porosity is preferably J J edible using, for example, a measuring device (trade name: Automated Perm-Porometer) manufactured by Porous Materials, Inc. in the United States.

(Pore direction)

The porous metal constituting the indwelling device of the present invention preferably has a pore directionality (Smax / Smin) of 2 or more. Further, the directionality (Smax / Smin) is preferably 10 or more, more preferably 20 or more (particularly 50 or more). The directionality of such pores can be suitably measured by the following method. <Method of measuring pore direction>

A hollow metal cylinder (before rolling, inner diameter of the porous metal: about 3 mm) having a hollow cylindrical shape is prepared along the axial direction of the porous metal as shown in the schematic perspective view of Fig. 5.

The porous metal tube obtained above is cut at one point along the pore axis direction, and a porous metal plate (thickness: about 1 mm, size: about 12 mm) as shown in the schematic perspective view of FIG. X about 20 mip).

The porous metal plate obtained above is cut to a thickness of about 1 mm along a direction perpendicular to the pore axis to obtain a porous metal fragment. Approximately 10 pieces of the metal pieces are arranged and adhered to each other using an epoxy resin to prepare a sample for measuring the directionality of pores made of porous metal pieces as shown in the schematic perspective view of FIG. Make this sample a suitable size (for example, Cut out with a disc of about 10 mm φ) and use for the following measurements. Using a device as shown in the schematic sectional view of FIG. 8, the W location water above the sample: the pressure of P = 1 3 3 X 1 0 5 P a (= 1 0 0 mm H g) was added Then, the amount of water passing through a predetermined area of the sample (for example, a disk having a diameter of about 7πιιηφ) is measured for about 5 minutes. Repeat the measurement about three times to find the average.

The measured value of the sample surface Α (that is, the surface through which water permeates in the direction in which the pore direction is maximum) is S max, and the sample surface B (that is, the direction in which water Calculate the pore directionality (Smax / Smin) with the measured value of the surface that transmits light as Sinin.

'(Mechanical strength)

The porous metal used in the present invention preferably has the following mechanical strength characteristics in view of its durability and reliability (particularly important in the medical field).

For example, the tensile strength (σ) in the direction parallel to the direction of the pores of the porous metal and the tensile strength (σ.) When the porosity of the porous metal is zero, that is, when the porous metal is solid (no pores) are measured. The ratio (Α) between the relative tensile strength (σΖσ) and the porosity (Ρ%) of the porous metal can be used as an index of mechanical strength.

A = {(σ / σ 0) / (1 0 0— Ρ)} X 1 0 0

In the present invention, される represented by the above formula is preferably 0.8 or more, more preferably 0.9 or more.

(Embodiment of indwelling device)

As long as the use of the porous metal is effective, the embodiment of the indwelling device of the present invention is not particularly limited. The indwelling device of the present invention typically includes, for example, artificial joints (FIG. 1), fracture fixing plates (FIG. 2), screws (FIG. 3), wires, and artificial dental roots (FIG. 4). Filling the cerebral aneurysm And a coil.

(Aspect of artificial joint)

FIG. 1 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial joint. This figure is an example of the so-called Changle type hip prosthesis. This artificial hip joint consists of a pelvis-side socket 1 that uses high-density polyethylene (HDP), ultra-high-density polyethylene (UH-MWPE), etc. as artificial cartilage, and a metal apex (pole) on the femur side. It consists of a part 2 and a metal stem 3. In FIG. 1, for example, when a porous metal (for example, a porous titanium alloy) is used as the stem, the weight of the base material is reduced, the impact force is absorbed, the affinity with the living body is increased, and infection is prevented. Benefits such as accelerating healing can be obtained.

(Form of fracture repair plate)

FIGS. 2 (a) and 2 (b) are a schematic plan view and a schematic cross-sectional view, respectively, showing an example in which the indwelling device of the present invention is used as a fracture repair plate. The fracture repair plate shown in FIG. 2 is an elongated member 4 that is slightly flat and has a desired number of holes 5. In FIG. 2, for example, when a porous metal (for example, a porous titanium alloy) is used as the elongated member 4, absorption of impact force and stress prevents the fixing screw from being loosened, Affinity, and can have advantages such as prevention of infection and promotion of healing.

(Mode of screw for fracture repair)

FIG. 3 is a schematic plan view showing an example in which the indwelling device of the present invention is in the form of a screw for repairing a fractured part. The screw for repairing a fracture in FIG. 3 has a handle 7 having a screw thread 6. In FIG. 3, for example, when the handle 7 is made of porous metal (for example, a porous titanium alloy), the screws are prevented from being loosened by absorbing the impact force, and the infection is prevented by improving the affinity with the living body. Can gain benefits such as promoting healing You.

(Aspect of artificial dental root)

FIG. 4 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial tooth root (implant). The artificial tooth root in FIG. 4 has a fixture 11 for fixing the artificial tooth to the gum 10, an attachment 12 for supporting the engagement, and an upper part having a shape similar to the shape of a human tooth. Having structure 13. In FIG. 4, for example, when a porous metal (for example, a porous titanium alloy) is used as an element, advantages such as prevention of infection due to strong bonding with gingival fibers and promotion of healing can be obtained. it can.

(Method of manufacturing porous metal)

The production method is not particularly limited as long as a porous metal having the above characteristics can be produced. In general, methods for producing a porous metal, such as a fabrication method, a plating method, a powder metallurgy method, and a sputter deposition method, have been developed as described below.

錶 construction method

Manufacturing methods include a melt foaming method, an interparticle infiltration method, and an investment method. In the molten metal foaming method, a physical method in which an inert gas or carbon dioxide gas is injected into the molten metal, agitated, foamed, and solidified, and a blowing agent such as a titanium hydride compound or a zirconium hydride compound is added to the molten metal. There is a chemical method that foams and solidifies with hydrogen gas generated by the decomposition reaction of hydrogen compounds. The porous structure obtained by these methods tends to be composed of independent pores, and it is relatively difficult to obtain a porous metal having anisotropic pores.

The interparticle infiltration method is a method in which molten metal is impregnated into gaps between small spheres packed in a mold and solidified, and hollow glass spheres or sodium chloride are often used for the small spheres. Small spheres made of sodium chloride After hardening, it can be dissolved with water. On the other hand, in the investment method, the voids of the polyurethane foam are filled with a refractory slurry, dried, and then fired to form a mold. After forming the molten metal under reduced pressure, the mold is removed to produce a porous metal.

Although the porous metal having a large pore size can be produced by the interparticle permeation method or the impregnation method, the pore diameter of a porous metal suitable for the stent of the present invention, that is, several μιη to several tens of It is relatively difficult to produce porous metal with a small pore size of μm. Further, the porous metal produced by the above method has a strong tendency that the pores become random and the mechanical properties deteriorate, and it is relatively difficult to process the obtained porous metal into a stent.

Mekko method

Draftite or the like is coated on the surface of the polyurethane foam skeleton by a chemical method, and this is used as a cathode. After nickel or the like is coated on the cathode in an electrolytic bath, the polyurethane foam is removed by firing to produce a porous metal. Also in this method, it is relatively difficult to produce a porous metal having a pore size suitable for the present invention and good mechanical strength.

Powder metallurgy method

A foaming agent is mixed with the slurry of the organic medium and the metal powder, foamed and solidified, and then fired. The slurry foaming method is not used, and the slurry is not subjected to HIP (hot isostatic treatment) or CIP (cold isostatic treatment). Pressure sintering method in which metal powder is sintered under pressure, sponge method in which polyurethane foam is immersed in a slurry of metal powder, dried, then pyrolyzed and sintered. .

Sputter deposition method

Using a sputtering method, gold was placed on a water-cooled substrate in an inert gas. The metal is sputter-deposited and a thin film is synthesized. Such a thin film usually contains about 20 to 2000 ppm of an inert gas. When the thin film is heated just below the melting point, bubbles formed by the mixed gas atoms are formed and grow, and the volume of the bubble is increased by heating to form a foamed metal.

As mentioned above, the production method of various porous metals or foamed metals has been outlined. Another new method is the metal-gas method described later. An open pore that can be suitably used for the porous metal for an indwelling device according to the present invention can be easily obtained, or the pore diameter is uniform, the pore directionality is small, and the pore diameter is as small as several μm to several hundred βm. From the viewpoint of easy control and the like, the metal-gas method can be particularly preferably used among the various methods described above.

Further, the porous metal obtained by the metal-gas method is of an open type and can be easily provided with anisotropic pores. By making use of the features of such pores, it is possible to achieve weight reduction while maintaining mechanical strength. Further, as described above, the body tissue can penetrate into the pore, and a strong bonding layer can be obtained between the metal material and the surrounding tissue. Further, by filling the pores with a functional substance (drug or bioactive substance, etc.), it becomes easy to provide a sustained release function, and to impart healing, antibacterial and other functions to the indwelling device of the present invention. It becomes possible to do.

(Metal-gas method).

Hereinafter, a method (metal-gas method) of imparting a porous structure that can be most suitably used in the present invention will be described.

In this method, using a metal-gas system, a porous metal is produced by utilizing the difference in solubility of gas atoms between a molten state and a solidified state of the metal (Japanese Patent Laid-Open No. 10-82854, Nippei 1 0— 2 2 7 6 2 4 No., Japanese Patent Application No. 1 1 1 4 2 5 7 5, Japanese Patent Application No. 11-195 5 260; Production and Technology, Vol. 51, No. 3, page 60 (1 9 9 9)). When metals are melted in a gas (hydrogen, oxygen or nitrogen) atmosphere, a large number of gas atoms dissociate and dissolve in the metal. Thereafter, when the molten metal is solidified, supersaturated gas atoms are precipitated, and pores are formed in the metal. Increasing the gas pressure when melting a metal in a gas atmosphere increases the solubility of gas atoms in the molten metal and increases the porosity.

On the other hand, the hole diameter and pore direction can be controlled by the cooling rate and cooling method of the molten metal. In this method, since the pore formation is based on the precipitation of supersaturated gas atoms, it is extremely easy to make the shape of the pore cross section of the porous metal substantially circular, for example. In such a porous metal having a substantially circular pore cross section, unlike a conventional porous metal having an irregular pore cross section, stress concentration does not occur around the pore at the time of deformation and a tensile stress is applied. In addition, it has been demonstrated that the “specific strength,” which is the stress divided by the effective cross-sectional area, does not depend on porosity (eg, SK Hyun et al. 〃Mechanical properties of porous copper fabricated by unidirect ional solidification under high pressure hydrogen, Proceeding of the International Conference on Solid-Solid Phase Tran sformation '99 (JIMIC-3), p. 341, edited by M. Koiwa et al., The Japan Institute of Materials, 19 9 9). In other words, even if the porosity of the porous metal having a substantially circular pore cross section is increased to some extent, the mechanical strength of the porous metal can be easily maintained.

The pores of the porous metal by the metal-gas method can be easily formed into open pores (that is, the pore openings are on the surface of the porous metal). Porous metal having such an open pore is a conventional porous metal. Unlike lath metal, it is easy to fill a drug or a physiologically active substance into the pore and release it slowly. .

The pores of the porous metal formed by the metal-gas method can be easily formed into a pore shape in which the directions of the pores are aligned in the axial direction, that is, a so-called “lotus root type pore”. It has been demonstrated that such a lotus root type pore has higher torsional strength and axial compressive strength than a solid (no pore) rod-shaped sample. Material Selection ”, pp. 149-153, translated by Junichi Kaneko and Masahisa Otsuka, published by Uchida Ritsuruho, 1977.

Furthermore, according to the experiments of the present inventor, the tensile strength of porous copper (porosity of about 30%) produced by using the metal-gas method is reduced by only 20 to 30%. It has been found that when about 30% of porous copper of porosidi is produced by the powder metallurgy method described above, the tensile strength tends to decrease by 60 to 90%. FIG. 9 is a graph showing an example of the relationship between porosity and σ / σ ₀ (relative tensile strength) of “Rotkon type” porous copper manufactured using the metal-gas method. As is clear from this graph, the above-mentioned “lencon-type” porous copper is superior to conventional sintered or foamed metal in strength at the same porosity.

(Material of porous metal)

The material of the porous metal is not particularly limited as long as a porous metal having the above-described characteristics can be manufactured. In the present invention, for example, iron, nickele, anorenium, copper, magnesium, konorenot, tungsten, manganese, chromium, beryllium, titanium, silver, gold and alloys thereof

(Hideo Nakajima, "Creation and Application of Porous Metals", Material Integration 12, 22, 37, 199 9). Stainless steel and Nitinol that are suitable for use as stent materials For example, it is possible to form a porous body using a metal-gas method.

(Inner surface of porous metal pore)

In the present invention, a modified layer (for example, a solid solution strengthening layer or a ceramic layer) may be formed on the inner surface of the pore of the porous metal as needed. For example, by increasing the hardness of the inner surface of the pores of the porous metal using the modified layer, the strength (tensile strength, compressive strength, bending strength, etc.) of the porous metal can be significantly improved.

As a method for forming such a modified layer on the inner surface of the pore of the porous metal, the following two methods can be used in the bay. .

(1) As described above, the porous metal in the present invention can be produced, for example, by utilizing the difference in the solubility of gas atoms in a molten state and a solidified state of a metal in a metal-gas system. Gas method). In this mode, when the molten metal is cooled and solidified, the solubility of gas atoms such as hydrogen, oxygen, and nitrogen in the metal decreases, and the gas phase separates from the metal phase to form pores. The solid solution strengthening layer can be easily formed by diffusing the gas atoms from the inner wall of the pore into the metal. By forming the solid solution strengthening layer, the hardness and the like of the inner surface of the pore can be improved.

(2) After preparing the porous metal of the present invention by various methods (for example, a metal-gas method), if necessary, a ceramic is formed on the inner surface of the porous metal pore by a known ceramic forming method. Layers can be formed. As such a ceramic forming method, a chemical vapor deposition method (chemical vapor deposition) or a physical vapor deposition method (physical vapor deposition; for example, ion implantation method) can be preferably used. is there.

In order to increase the hardness of the inner surface of the pore, a ceramic such as titanium nitride (TiN) or titanium carpide (TiC) is used. The formation of a layer is effective. For example, TiN or TiC is formed on the inner surface of a porous metal by using titanium as an evaporation source and using nitrogen or acetylene as a reaction gas element by an ion plating method. It is possible. When such a ceramic layer is formed on the inner surface of the porous metal, for example, the thickness of the ceramic layer is adjusted to 100 by controlling the vapor deposition conditions. It can be controlled in the range of A (Angstrom) to several μm.

(Production of indwelling device using porous metal)

The method for imparting the indwelling device shape to the porous metal described above is not particularly limited, and a known method can be used.

For example, in the above-described embodiment using the metal-gas method, a supersaturated gas is precipitated in a solid phase in a process of dissolving a gas in a molten metal material, and then solidifying and transforming the solid into a solid. Porous metal is produced by using this property, and used as a base material for indwelling devices.

Examples of a method for producing an indwelling device using the porous metal include a method using a linear porous metal and a method of finishing a desired shape by cutting a plate-shaped or rod-shaped porous metal. . Fracture fixation wires, cerebral aneurysm ligation clips, cerebral aneurysm filling coils, etc. are also produced from the former, and fracture fixation plates, screws, artificial dental roots, etc. are made by the latter method. it can.

(Portion of indwelling device using porous metal)

All or a part of the metal part constituting the indwelling device of the present invention can be basically made of a porous metal. In the following embodiment of the device for indwelling in a body, a portion particularly preferably constituted by a porous metal is exemplified as follows.

Artificial joints (Fig. 1, embodiment, etc.): Metal stem part 3

Fracture fixation plate (as shown in Fig. 2, etc.): Plate body 4 Fracture fixing screw (as shown in Fig. 2, etc.): Screw with screw thread 6 Body 7

Fracture fixation wire: Wire body

Artificial dental roots (as in Fig. 3, etc.): Fixtures 11 and 11

Clip for ligation of cerebral aneurysm: Clip body

Cerebral aneurysm filling coil: Coil body

(Production of stent using porous metal)

The method for imparting the stent shape to the porous metal is not particularly limited, and a known method can be used.

For example, in the above-described embodiment using the metal-gas method, a supersaturated gas is precipitated in a solid phase in a process of dissolving a gas in a molten metal material, and then solidifying and transforming the solid into a solid. The porous metal is produced by using the property that the metal is used as the base material of the stent.

Examples of a method for producing a stent using the porous metal include a method using a linear porous metal and a method of finishing a cylindrical porous metal into a desired shape by cutting. A coil stent is manufactured from the former, and a slotted tube stent is manufactured from the latter.

(Production method of linear porous metal)

FIG. 10 is a schematic cross-sectional view showing an example of an apparatus for producing a linear porous metal.

Referring to FIG. 10, a ceramic crucible 21 having a nozzle 21 a is filled with a material such as stainless steel, tantalum, titanium, an alloy of titanium and nickel (Nitinol), and high-frequency heating 2 2 Heat is applied from the periphery by such means as heating and melting. At this time, the atmosphere is hydrogen, oxygen, nitrogen, or a mixed gas of them with an inert gas such as argon or helium. Dissolve hydrogen, oxygen, or nitrogen gas atoms in the molten metal (or alloy) 24 using Thereafter, a slight pressure is applied to the crucible 21 to cause the molten metal to flow out of the nozzle 21a, and the molten metal is brought into contact with a cooling unit 25 provided at a lower portion of the nozzle 21a, thereby passing through the nozzle. While maintaining the shape of the released linear molten metal, the molten metal is solidified at a predetermined solidification rate to produce a thin wire 26. By reducing the diameter of the nozzle 21a, it is possible to produce a considerably long thin wire 26. By changing the diameter of the nozzle, the thickness of the porous fine metal wire 26 can be easily changed. In addition, the solidification rate can be controlled by controlling the temperature and flow rate of the cooling medium circulating in the cooling section, or by installing a heating section in the cooling section 25, whereby the pores can be controlled. It is possible to freely control the size, length (pore aspect ratio), porosity, and angle between the linear busbar and the pore growth direction. Since the surface of the porous fine metal wire 26 generated in this manner has an extremely high cooling rate, pores cannot normally be generated on the surface of the fine wire, and a nonporous surface is formed. . For this purpose, if necessary, the non-polar surface of the fine wire may be removed by a chemical polishing method such as corrosion etching using an acid solution, or a physical or mechanical polishing method such as sand polishing or mechanical cutting.

After such treatment, the final shape of the porous fine metal wire 26 is, for example, as shown in Fig. 11, with pores exposed on the surface and growing with a slight inclination in the direction of the fine wire bus. It will be. In order to smooth the surface of the fine wire 26, drawing plastic working may be performed as necessary to form a fine wire having a uniform diameter. This process is not merely to make the thickness uniform, but also to introduce new plasticity into the thin wire 26 to refine the crystal grains. There is an advantage that the strength of the fine wire can be enhanced by introducing the stub.

(Production method of plate-shaped or rod-shaped porous metal)

FIG. 12 is a schematic cross-sectional view showing an example of an apparatus for producing a cylindrical porous metal. Referring to Fig. 12, a ceramic crucible 32 is filled with starting materials 31a, such as stainless steel, tantalum, titanium, and an alloy of titanium and nickel (Nitinol), and a high-frequency heating coil 33 Heat is melted by applying heat from the surroundings. The crucible 32 is surrounded by a heat insulator 34, a heat shield 35, and a pressure vessel 36. When the above-mentioned starting material 31 a is heated and melted, molten metal (or alloy) 3 is used as atmosphere 31 c using hydrogen, oxygen, nitrogen or a mixed gas thereof with an inert gas such as argon or helium. Dissolve hydrogen, oxygen, or nitrogen gas atoms in lb. Thereafter, the apparatus is tilted by 90 degrees, and molten metal 31b is poured into mold 38 through pouring funnel 37. Since the cooling part 39 is installed on the bottom of the mold 38, solidification of the molten metal proceeds from the bottom (cooling part 39 side) upward (to the pouring funnel 37 side). . That is, by using such an apparatus, it is possible to cause the solidification of the molten metal and “unidirectional solidification” upward. In such unidirectional solidification, it is extremely easy to change the pore size, length, porosity, etc. by controlling the solidification rate and atmospheric gas pressure.

For example, the above-prepared porcelain metal produced as described above is cut into a plate shape or a rod shape and cut and plastically processed. In this case, if necessary, it can be rolled at the stage of cutting out into a porcelain porous metal or a plate or a rod, and then subjected to plastic working to refine the crystal grains and strengthen the base material by plastic strain. It is.

In addition, as described above, the porous metal manufacturing process (metal- In the gas method, gas atoms such as oxygen or nitrogen usually react with the metal to form a solid solution oxygen or nitrogen-enriched layer on the inner surface of the pore of the porous metal. As a result, a porous metal having high strength can be easily obtained.

Further, after the porous metal is produced by the above method, if necessary, the inner surface of the pore of the porous metal is formed using a chemical vapor deposition method or a physical vapor deposition method (such as an ion plantation method). By forming a ceramic layer such as titanium nitride or titanium carbide having excellent hardness, a porous metal having further excellent mechanical properties can be obtained.

As shown in the graph of FIG. 13, when the above metal-gas method is used, the growth amount and morphology of the pores in the porous metal, that is, the formation of the pore direction, size, porosity, etc. are determined by the melting temperature, the melting point, Parameters such as gas pressure, solidification gas pressure, cooling temperature, solidification cooling rate, and mixing volume ratio with inert gas-pressure can be freely and accurately controlled and determined. The graph in Fig. 13 shows that one-way multicore pores are formed by solidifying nitrogen gas into iron melted at about 650 ° C under the pressure of a mixture of nitrogen and argon, respectively. is represented by the relationship between the porosity of the porous iron was produced (%) and nitrogen gas partial pressure (P- N ₂₎ and argon gas partial压(P- a r).

Figures 14 to 17 show optical micrographs (magnification: 2.6 times) of cross sections of porous iron obtained by the ratio of the partial pressures of nitrogen gas and argon gas shown in the graph of Figure 13 respectively. It is. According to these figures, the porosity changes depending on the ratio of the partial pressure of nitrogen gas to the partial pressure of argon gas, and the porosity increases as the nitrogen gas pressure increases relative to the argon gas pressure. You can understand that.

(Non-metallic substances) The in-vivo indwelling device of the present invention comprising the above-described porous metal can be filled with various nonmetallic substances, if necessary. Use of such a nonmetallic substance, a functional material capable of exerting various functions, and imparting useful functions to the in-vivo indwelling device by carrying it in the pore and releasing it or releasing it slowly can do.

The nonmetallic substance to be filled in the pores of the porous metal is not particularly limited as long as the function of the indwelling device of the present invention comprising a porous metal is not substantially impaired. The nonmetallic substance preferably contains an organic substance from the viewpoint of easy filling into the pores and easy provision of functionality.

Examples of such an organic substance include a drug or a physiologically active substance. By filling the porous material into the pores of the porous metal, the indwelling device of the present invention can carry a drug or a physiologically active substance and / or sustained release. There is no particular limitation on the drug or bioactive substance to be filled in the pore, and one or more known drugs or bioactive substances can be appropriately selected or used in combination.

Examples of such drugs or physiologically active substances include thrombus formation inhibition, thrombolysis, platelet adhesion / aggregation inhibition, infection prevention, anticancer properties, growth inhibition of fibroblasts / smooth muscle cells, vascular endothelium, etc. Substances having the ability to promote proliferation of cells and the like can be mentioned.

(Cell)

The bone cells or the like of the patient itself can be suitably used as necessary for the plate for fixing a fractured part or the artificial dental root. In the case of an aneurysm filling coil or the like, a stem cell capable of differentiating into a vascular endothelial cell or a vascular endothelial cell is preferably used to promote vascular endothelialization.

(Polymer material)

In an embodiment in which the above-mentioned drug or physiologically active substance is filled in the pores of the indwelling device of the present invention made of porous metal, In order to release the drug or bioactive substance at a predetermined elution rate for a predetermined period, it is preferable to combine a drug or a physiologically active substance with a polymer material. A suitable polymer material can be selected depending on the solubility of the drug or the physiologically active substance to be filled in blood, the molecular weight, the physiologically active concentration, the release period, and the like. As one of suitable polymer materials, there is a polymer material having biodegradability. Examples of the biodegradable polymer material include biodegradable polyesters typified by polydicalic acid, polylactic acid, various polylactones, and the like. In addition, the drug or physiologically active substance incorporated in the high molecular material elutes from the surface of the material, so that the porous polymer material, in particular, the hydrogel (a hydrous liquid to be retained inside is substantially lost) Or a so-called “xerogel” state) or a polymer having a mouth-opening gel-forming property. Examples of the gel for the mouth opening include natural gels such as collagen gel, gelatin gel, fiprimin gel, matrigel, genole alginate, chitosan gel, hyaluronic acid gel and various synthetic polymer hydrogels. Is mentioned.

On the other hand, as a polymer material for immobilizing cells (for example, bone cells for promoting bone formation or vascular endothelial cells for promoting vascular endothelialization), the activity of cells inside the polymer material is maintained. It is highly preferred that nutrients can be easily replenished and waste products removed so that they can be divided and propagated. From this point, a hide-mouth gel can be particularly preferably used as a polymer material for immobilizing cells. In particular, the above-mentioned natural product hydrogel, and a gelling type thermoreversible individual dydrogene at the time of heating, which becomes a solution state at a low temperature and a gel state at a high temperature (Yoshioka, H. et al, "Preparation of poly (N. -isopropylacylacrylamide)-block-poly (ethylene glycol) and calorimetric analysis of its aqueous solution ", J. Mac Sci., 31, 109, 1994). (Method of filling non-metallic material into porous metal pores)

The method of filling a nonmetallic substance (for example, a drug, a physiologically active substance or a cell) into the pore of the indwelling device made of the porous metal of the present invention in combination with a high molecular material as necessary is not particularly limited. It can be appropriately selected from known methods or used in combination. For example, as a method of combining a drug or a physiologically active substance with a polymer material, a mixed solution in which both are dissolved or dispersed in water or an organic solvent is prepared, and the mixed solution is prepared from the porous metal of the present invention. The most common method is to immerse the indwelling device. In this case, for example, the air in the pores of the indwelling device is replaced with a mixed solution under negative pressure, and the indwelling device is taken out and dried to remove water or an organic solvent. Non-metallic material can be filled into the pores of the detention tool. -On the other hand, as a method of combining cells and the like with the above-mentioned hydrogel, for example, in the case of collagen, the cells are dispersed in a solution containing a hydrogel-forming polymer, and the dispersion is used in a device for indwelling the body. After the introduction into the pore, by changing the pH or the temperature, the hydrogel-forming polymer can be gelled and the cells can be immobilized in the gel. In the case of alginic acid gel, cells are dispersed in a medium solution of sodium alginate, and the dispersion is introduced into the pores of the indwelling device, and then, for example, contacted with a concentrated calcium chloride solution. The alginate soda can be gelled and the cells can be immobilized in the pore.

In addition, in the case of the above-mentioned gelled thermoreversible hydrogel at the time of temperature rise, cells are dispersed in a solution state in which the hydrogel-forming polymer is dissolved at a low temperature, and the cell dispersion is placed in a pore of an indwelling device. After filling inside, The cells can be immobilized by increasing the degree of gelation of the polymer having a gel-forming mouth opening to a higher degree. The sol-gel transition temperature of the gelled thermoreversible hide opening gel at the time of temperature rise is preferably within the physiological temperature range of cells. Industrial applicability

As described above, the indwelling device according to the present invention not only has excellent strength and lightness due to the porous metallic material constituting the device, but also has a remarkably increased contact area with internal tissues. Sufficient bonding strength can be easily obtained.

Furthermore, in the embodiment of the present invention using the porous metal having the above-described anisotropic pore structure, the indwelling device not only has excellent mechanical strength but also exhibits toughness similar to hard tissue in the body. Becomes easier. Further, in the indwelling device of the present invention having the above structure, since the metal material constituting the device is porous (especially in the case of the above-described anisotropic pore structure), the in-vivo tissue can easily enter the inside thereof. It is easy to strengthen the bond between the metal material and the surrounding body tissue. In this case, since the size of the pore can be controlled so that the body tissue can enter the pore, the degree of penetration of the body tissue can be controlled by the size of the pore. When the indwelling device is firmly held in the body in this way, infection that may occur at the joint can be effectively prevented.

In addition, it is easy to carry various physiologically active substances in the porous metal pore of the present invention and to release the same in a sustained manner, whereby the in-vivo indwelling device of the present invention has high functions (for example, healing promoting action, Antibacterial action, anti-hemolytic action, thrombus forming action, etc.).

As described above, it has excellent mechanical properties obtained by the present invention. The stent formed by the porous metal can prevent the stent itself from being weakened or peeling the coating material from the stent main body as much as possible, and the non-metal can be contained in the pores of the porous metal constituting the stent. It is very easy to fill the substance. Therefore, by filling various functional substances such as organic substances as the non-metallic substance, it is extremely easy to impart a desired function to the whole indwelling device (stain or the like) of the present invention. Becomes In the present invention, since the porous metal itself constituting the stent has a porous structure, even when the stent is filled with a nonmetallic substance, the stent itself as in the case of a polymer material is used. This makes it possible to suppress the weakening of the coating material and the peeling off of the coating substance from the stent body as much as possible. In this case, it becomes possible to release these substances from the pores. Alternatively, it is also possible to fill the pores with vascular endothelial cells or stem cells supported on hydrogel or the like. Therefore, according to this aspect, it is possible to solve the conventional problems such as thrombus formation at the initial stage of stent placement and restenosis or re-occlusion due to hyperproliferation of the vascular intima at the late stage of placement. .

Further, in the embodiment of the present invention in which the porous metal is produced by utilizing the difference in solubility of gas atoms in a molten state and a solidified state of a metal in a metal-gas system, the open pores and the orientation are uniform. It is possible to easily obtain pores and / or pores having a solid solution strengthening layer or a ceramic layer having excellent hardness on the inner surface. Therefore, as a stent formed from the porous metal, a stent having excellent mechanical properties, preventing recoil of a blood vessel wall, etc., and exhibiting excellent durability against repeated stretching and contraction movements of a blood vessel wall, etc., can be easily obtained. Obtainable.

Claims

Range of request

1. An indwelling device that contains a metal part at least in part

A device for indwelling the body, wherein at least a part of the metal part contains a porous metal

2. The indwelling device according to claim 1, wherein the porous metal has anisotropic pores (pores).

3. The in-vivo indwelling device according to claim 2, wherein the porous metal has an anisotropic pore of 2 or more in a ratio (Smax / Smin) of the maximum value Z minimum value indicating the pore directionality.

4. The indwelling device according to claim 2, wherein the pores of the porous metal are mainly open pores.

5. The in-vivo indwelling device according to any one of claims 2 to 4, wherein pore directions of the porous metal are aligned in one direction.

6. The indwelling device according to any one of 2 to 5, wherein a shape of a pore cross section orthogonal to a direction of the porous metal is substantially circular.

7. The indwelling device according to any one of claims 1 to 6, wherein an inner surface of the porous metal pore is formed of a solid solution strengthening layer or a ceramic layer.

8. The indwelling device according to any one of claims 1 to 6, wherein a non-metallic substance is filled in the pores of the porous metal.

9. The indwelling device according to claim 8, wherein the non-metallic substance is a drug, a physiologically active substance, or a cell.

10. The in-vivo indwelling device according to claim 8 or 9, wherein the non-metallic substance is filled in a state of being combined with a polymer material.

11. The body according to any one of claims 1 to 10, wherein the porous metal is produced by utilizing a difference in solubility of gas atoms between a molten state and a solidified state of the metal using a metal-gas method. For indwelling medical use.

12. The inner surface of pores of the porous metal is a solid solution strengthening layer, and the solid solution strengthening layer is formed by a reaction between the metal atom and a gas atom in a step of producing the porous metal. 2. The indwelling device according to claim 1.

13. The method according to claim 7, wherein an inner surface of the pore of the porous metal is a ceramic layer, and the ceramic layer is formed by a chemical vapor deposition method or a physical vapor deposition method. In-vivo tools.

14. The indwelling device according to claim 7, wherein an inner surface of the pore of the porous metal is a ceramic layer, and the ceramic layer is formed by an ion plantation method. ·

15. The in-vivo indwelling device is in the form of an indwelling device in hard tissue selected from an artificial bone, a fracture-fixing plate, a fracture-fixing screw, a fracture-fixing wire, and an artificial root. 14. The indwelling device according to any one of 14 to 14.

16. The in-vivo indwelling device is in the form of an intra-cerebral artery indwelling device selected from a cerebral aneurysm ligation clip and a cerebral aneurysm filling coil. Indwelling device.

17. The indwelling device according to any one of claims 1 to 14, wherein the indwelling device is in the form of a stent.